The brain processes sensory stimuli differently depending on whether an animal is awake or anesthetized. In anesthetized animals no internal cognitive activity influences the brain, and so stimuli are passively received and coded solely for their physical properties. In awake subjects, on the other hand, responses to stimuli are heavily modulated by ongoing mental processes (i.e. attention, expectation). The same stimulus, for instance, is interpreted differently depending on what the animal expects: humans - and their brains - led to expect a mild taste, for instance, can be "fooled" into thinking that a bitter taste is milder than it actually is. The present proposal is designed to study the neural underpinnings of such phenomena: in particular, the experiments outlined here will address the extent to which expectation influences background activity of the brain and responses to sensory stimuli. The intrinsic rewarding/aversive nature of gustatory stimuli and the importance of food selection for animal survival make taste an ideal sensory system for directly studying the effects of expectation at both the neural and behavioral level. The experiments proposed will be conducted in awake rats;ensembles of single neurons will be recorded with multiple electrodes implanted in areas known to be involved in taste and expectation (GC, orbitofrontal cortex [OFC], amygdala [AM]). Two different aspects of expectation will be investigated: generic expectation of an unknown stimulus (a process somewhat analogous to attention) and specific expectation of a known stimulus. For the first, rats will be trained to collect a taste by pressing a lever in response to a tone. In this paradigm, the tone will not provide any information regarding the identity of the taste-it will simply trigger an attentional shift related to the expectation of an unknown stimulus. Expectation of a specific stimulus, on the other hand, will be addressed in another subset of experiments involving the use of two tones, each specifically associated with a different taste. In these experiments, the auditory cues will provide information about the specific taste anticipated. Spontaneous activity, responses to anticipatory cues, and responses to unexpected and expected tastes will be recorded to parse the effects of generic and specific expectation on taste. Finally, electrodes will be implanted also in OFC and AM - two areas known to be involved in expectation - and the relationship between these two areas and GC will be studied in the experimental conditions described above. Understanding the degree to which internal states, such as expectation, shape sensory responses is a central question in the field of sensory neuroscience. The comprehension of how the brain responds to the expectation of tastes will shed light on the complexities of food selection choices of all mammals - including humans - and will provide important information which could potentially be applied to the study of obesity and eating disorders. This proposal is designed to understand the neural underpinnings of expectation of taste stimuli. Expectation plays an important role in the perception of food and in its evaluation (Deliza and MacFie 1996;Hurling and Shepherd 2003);as such, this subject has important implications on issues relevant to public health, such as food liking and selection choices. Additionally, understanding the neural basis of expectation is relevant for the study of the neural mechanisms of placebo (Nitschke et al. 2006a;Nitschke et al. 2006b;Sarinopoulos et al. 2006) - a growing field of interest in neuroscience (Petrovic et al. 2005;Ploghaus et al. 1999).